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1.
Mol Ther ; 30(6): 2130-2152, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35149193

RESUMO

Immunotherapy with antigen-specific T cells is a promising, targeted therapeutic option for patients with cancer as well as for immunocompromised patients with virus infections. In this review, we characterize and compare current manufacturing protocols for the generation of T cells specific to viral and non-viral tumor-associated antigens. Specifically, we discuss: (1) the different methodologies to expand virus-specific T cell and non-viral tumor-associated antigen-specific T cell products, (2) an overview of the immunological principles involved when developing such manufacturing protocols, and (3) proposed standardized methodologies for the generation of polyclonal, polyfunctional antigen-specific T cells irrespective of donor source. Ex vivo expanded cells have been safely administered to treat numerous patients with virus-associated malignancies, hematologic malignancies, and solid tumors. Hence, we have performed a comprehensive review of the clinical trial results evaluating the safety, feasibility, and efficacy of these products in the clinic. In summary, this review seeks to provide new insights regarding antigen-specific T cell technology to benefit a rapidly expanding T cell therapy field.


Assuntos
Neoplasias , Viroses , Antígenos de Neoplasias , Humanos , Imunoterapia/métodos , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Linfócitos T
2.
Adv Healthc Mater ; : e2400378, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621382

RESUMO

In the pursuit to combat stubborn bacterial infections, particularly those stemming from gram-positive bacteria, this study is an attempt to craft a precision-driven platform characterized by unparalleled selectivity, specificity, and synergistic antimicrobial mechanisms. Leveraging remarkable potential of metalloantibiotics in antimicrobial applications, herein, this work rationally designs, synthesizes, and characterizes a new library of Pyridine-2,6-dicarboxamide ligands and their corresponding transition metal Cu(II)/Zn(II) complexes. The lead compound L11 demonstrates robust antibacterial properties against Staphylococcus aureus (Minimum Inhibitory Concentration (MIC) = 2-16 µg mL-1), methicillin and vancomycin-resistant S. aureus (MIC = 2-4 µg mL-1) and exhibit superior antibacterial activity when compared to FDA-approved vancomycin, the drug of last resort. Additionally, the compound exhibits notable antimicrobial efficacy against resistant enterococcus strains (MIC = 2-8 µg mL-1). To unravel mechanistic profile, advanced imaging techniques including SEM and AFM are harnessed, collectively suggesting a mechanistic pathway involving cell wall disruption. Live/dead fluorescence studies further confirm efficacy of L11 and its complexes against S. aureus membranes. This translational exploration extends to a rat model, indicating promising in vivo therapeutic potential. Thus, this comprehensive research initiative has capabilities to transcends the confines of this laboratory, heralding a pivotal step toward combatting antibiotic-resistant pathogens and advancing the frontiers of metalloantibiotics-based therapy with a profound clinical implication.

3.
Curr Pharm Biotechnol ; 24(9): 1149-1163, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36177622

RESUMO

By helping practitioners understand complicated and varied types of data, Artificial Intelligence (AI) has influenced medical practice deeply. It is the use of a computer to mimic intelligent behaviour. Many medical professions, particularly those reliant on imaging or surgery, are progressively developing AI. While AI cognitive component outperforms human intellect, it lacks awareness, emotions, intuition, and adaptability. With minimum human participation, AI is quickly growing in healthcare, and numerous AI applications have been created to address current issues. This article explains AI, its various elements and how to utilize them in healthcare. It also offers practical suggestions for developing an AI strategy to assist the digital healthcare transition.


Assuntos
Inteligência Artificial , Transição para Assistência do Adulto , Humanos
4.
Artigo em Inglês | MEDLINE | ID: mdl-37231727

RESUMO

Currently, there are no approved treatments for the fatal infectious coronavirus disease. The process of identifying new applications for approved pharmaceuticals is called drug repurposing. It is a very successful strategy for drug development as it takes less time and cost to uncover a therapeutic agent than the de novo procedure. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the seventh coronavirus that has been identified as a causative agent in humans. SARS-CoV-2 has been recorded in 213 countries, with over 31 million confirmed cases and an estimated death rate of 3%. Medication repositioning may indeed be regarded as a unique therapeutic option for COVID-19 in the present situation. There are various drugs and techniques, which are being used to treat the symptoms of COVID-19. These agents are directed against the viral replication cycle, viral entrance, and viral translocation to the nucleus. Additionally, some can boost the innate antiviral immune response. Drug repurposing is a sensible method and could be a vital approach to treating COVID-19. Combining some of the drugs or supplements with an immunomodulatory diet, psychological assistance, and adherence to standards can ultimately act against COVID-19. A better knowledge of the virus itself and its enzymes will enable the development of more precise and efficient direct-acting antivirals. The primary aim of this review is to present the various aspects of this disease, including various strategies against COVID-19.

5.
Artigo em Inglês | MEDLINE | ID: mdl-37807405

RESUMO

BACKGROUND: Organoids are in vitro models that exhibit a three-dimensional structure and effectively replicate the structural and physiological features of human organs. OBJECTIVE: This work examines the potential applications of organoid technology, as well as the challenges and future directions associated with its implementation. METHODS: The manuscript was put together by conducting a comprehensive literature review, which involved an in-depth evaluation of globally renowned scientific research databases. RESULTS: The field of organoids has generated significant attention due to its potential applications in tissue development and disease modelling, as well as its implications for personalised medicine, drug screening, and cell-based therapies. The utilisation of organoids has proven to be effective in the examination of various conditions, encompassing genetic disorders, cancer, neurodevelopmental disorders and infectious diseases. CONCLUSION: The exploration of the wider uses of organoids is still in its early phases. Research shall be conducted to integrate 3D organoid systems as alternatives for current models, potentially improving both fundamental and clinical studies in the future.

6.
Chem Commun (Camb) ; 59(96): 14305-14308, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37970743

RESUMO

Chemodynamic therapy is an evolving therapeutic strategy but there are certain limitations associated with its treatment. Herein, we present de novo synthesis and mechanistic evaluation of HL1-HL8 ligands and their corresponding CuII(L1)2-CuII(L8)2. The most active Cu(L2)2 (IC50 = 5.3 µM, MCF-7) complex exclusively depletes glutathione while simultaneously promoting ROS production. Cu(L2)2 also affects other macromolecules like the mitochondrial membrane and DNA while activating the unfolded protein response cascade.


Assuntos
Glutationa , Peróxido de Hidrogênio , Glutationa/metabolismo , Linhagem Celular Tumoral
7.
Bioresour Technol ; 188: 280-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25603730

RESUMO

Hydrothermal liquefaction of rice straw has been carried out using various organic solvents (CH3OH, C2H5OH) at different temperatures (250, 280 and 300 °C) and residence times (15, 30 and 60 min) to understand the effect of solvent and various reaction parameters on product distribution. Maximum liquid product yield (47.52 wt%) was observed using ethanol at 300 °C and 15 min reaction time. FTIR and NMR ((1)H and (13)C) of liquid product indicate that lignin in rice straw was converted to various monomeric phenols. GC-MS of the liquid product showed the presence of various phenol and guaiacol derivatives. Main compounds observed in liquid product were phenol, 4-ethylphenol, 4-ethyl-2-methoxyphenol (4-ethylguaiacol), 2,6-dimethoxyphenol (syringol), 2-isopropyl-5-methylphenol (thymol). Powder XRD and SEM of bio-residue showed that rice straw was decomposed to low molecular weight monomeric phenols.


Assuntos
Lignina/química , Metanol/química , Oryza/química , Fenol/química , Biomassa , Etanol/química , Cromatografia Gasosa-Espectrometria de Massas , Guaiacol/análogos & derivados , Guaiacol/química , Hidrocarbonetos/química , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Fenóis/química , Pirogalol/análogos & derivados , Pirogalol/química , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Timol/química , Água/química , Difração de Raios X
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